To the best of our knowledge, this study is the first to assess the impact of EPA + DHA supplementation on the expression of inflammatory genes in duodenal tissues of obese patients with type 2 diabetes.
Our results first showed that the expression of inflammatory genes in duodenal tissues of obese men with type 2 diabetes is relatively low, particularly in the case of IL-6 and TNF-α. This suggests that inflammation at the level of duodenal cells per se may not play a significant role in modulating chronic low-grade inflammation in obese diabetic patients. As reviewed by Ding and Lund , very little is known on the crosstalk between the intestine and adipose tissue in fostering chronic inflammation. In the case of Crohn’s disease, the extent of inflammation and cellular damage has been correlated with the accrual of mesenteric fat around the intestine (so-called “creeping” fat) . As is the case with abdominal fat, mesenteric fat is characterized by infiltration with immune cells and increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α . The duodenal biopsy procedure in the present study collected basolateral cells and not cellular material from the outer surface of the intestine where mesenteric fat would be found. Thus, our study cannot resolve the possibility that mesenteric fat expresses pro-inflammatory genes in type 2 diabetes.
Our study also suggests that 3 g/d EPA + DHA supplementation has no impact on duodenal cells gene expression of pro-inflammatory cytokines and of transcription factor STAT3 compared with a placebo. Previous studies in animal models have shown that LCn-3PUFA from fish oil down-regulate the small intestine and gut-associated lymphoid tissue expression of inflammatory mediators (interferon-γ, chemokines) [19, 20]. Other recent studies in cell culture and animal models also suggest that LCn-3PUFA down-regulate inflammatory gene expression by modifying the activity of transcription factors such as nuclear factor-κB and peroxisome proliferator-activated receptor-γ, which are expressed in the gastrointestinal tract . The lack of effect of LCn-3PUFA supplementation on mRNA expression of pro-inflammatory cytokines and of transcription factor STAT3 in duodenal tissues of obese patients with type 2 diabetes in the present study is most likely attributable to the fact that gene expression was extremely low and therefore unlikely to be further modified. However, consistent with our results, a study performed in 242 human subjects by Pot et al.  has shown that concentrations of local markers of inflammation measured in biopsy samples of the colon were unaffected by consumption of oily fish, which represents a naturally occurring source of EPA + DHA.
A limitation that needs to be pointed out is the limited number of subjects which yielded limited statistical power to detect treatment differences in gene expression. However, mRNA expression levels of inflammatory genes were very low in most cases, and it is unlikely that such numbers would have changed with a larger sample size. The use of a randomized crossover design is strength and the long intervention and washout periods have limited the possibility of a carry-over effect of the LCn-3PUFA supplementation. Analyses of plasma fatty acid profiles following placebo and EPA + DHA supplementation confirmed compliance to treatments.
In summary, we believe this is the first study suggesting that gene expression of pro-inflammatory cytokines in duodenal tissues from obese patients with type 2 diabetes is very low and not affected by EPA + DHA supplementation. Further studies will be needed to investigate if inflammatory gene expression in other tissues surrounding the intestine such as mesenteric fat is modulated by EPA + DHA supplementation.